Dose-Response Relationship of Oral Insulin Spray in Healthy Subjects

• Published in: Diabetes care Vol. 28; no. 6; pp. 1353 - 1357
• Main Authors: Cernea, Simona, Kidron, Miriam, Wohlgelernter, Jay, Modi, Pankaj, Raz, Itamar
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2005
• Subjects: Administration, Oral; Adult; Analysis of Variance; Area Under Curve; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Body Mass Index; Cross-Over Studies; Diabetes; Diabetes. Impaired glucose tolerance; Dosage and administration; Dose-Response Relationship, Drug; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Glucose; Glucose Clamp Technique; Humans; Insulin; Insulin - administration & dosage; Insulin - blood; Insulin - pharmacology; Intestinal Absorption; Medical sciences; Metabolism; Pharmacology; Reference Values; United States; Pancreatic hormone; Healthy subject; Insulin; Oral administration; Dose activity relation
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.28.6.1353

OBJECTIVE:--To evaluate the pharmacodynamic and pharmacokinetic properties and the dose-ranging effects of an oral insulin spray in comparison with subcutaneous regular insulin. RESEARCH DESIGN AND METHODS--In this randomized, five-way, cross-over study, seven healthy volunteers were assessed under euglycemic clamp and received four different doses of oral spray and one dose of subcutaneous regular insulin. RESULTS:--The time to maximum insulin concentration was shorter for oral insulin than for subcutaneous insulin (25.9 ± 9 vs. 145.7 ± 49.5 min, P < 0.05). Maximum serum insulin levels (C[subscript max]) were comparable between the subcutaneous and 20 puffs of oral insulin (39.1 ± 19.6 vs. 34.0 ± 7.4 [micro]U/ml, NS). The Ins-AUC₀₋₁₂₀ (area under the curve from 0 to 120 min for serum insulin) (339.8 ± 218, 681.3 ± 407, and 1,586.7 ± 8 [micro]U/ml, P < 0.05) and C[subscript max] (7.6 ± 2.8, 16.4 ± 9.3, and 39.1 ± 19.6 [micro]U/ml, P < 0.005) proved a dose-response relationship for the three doses of oral insulin (5, 10, and 20 puffs, respectively). Oral insulin had an earlier onset of action (31.7 ± 12 vs. 77.8 ± 3 min, P < 0.05), earlier peak (44.2 ± 10 vs. 159.2 ± 68 min, P < 0.05), and a shorter duration of action (85.1 ± 25 vs. 319.2 ± 45 min, P < 0.05) compared with subcutaneous insulin. The maximum metabolic effect (1.7 ± 1.0, 3.09 ± 1.7, and 4.6 ± 1.5 mg · kg⁻¹ · min⁻¹, P < 0.05) and the GIR-AUC₀₋₁₂₀ (amount of glucose infused from 0 to 120 min) (106.7 ± 74.3, 162.9 ± 116.1, and 254 ± 123 mg/kg) increased in a dose-dependent relationship for the three doses. CONCLUSIONS:--Oral insulin was absorbed in direct relation to the amount given and had a faster onset and a shorter duration of action compared with subcutaneous regular insulin. A dose-response relationship in the absorption and metabolic effect of the oral insulin was noted.